The proposed research is a multidisciplinary investigation of the regulation of the neuronal phenotype and, in particular, a study of the interrelationship between the morphological and biochemical properties distinct to neurons. Using biochemical, immunochemical, morphological, genetic, and tissue culture techniques, this project will examine three aspects of this relationship: Firstly, using human neuroblastoma cells, I will examine the regulation of the neuronal phenotype during differentiation of a non-neuronal, epithelial-like cell into a neuroblast-like cell. The aim of this project is to determine if the changes in the cell's morphology and biochemistry are coordinately regulated and what factors might influence the direction and speed of this interconversion. Secondly, using biochemical assyas for the neurotransmitter enzymes, e.g. tyrosine hydroxylase, I will examine the effects of growth and cell-to-cell contract on the regulation of the neuronal phenotype. Specifically, this study will investigate the components of the cell surface or in the culture medium which regulates the level of neurotransmitter enzyme within the cell. Finally, using fetal superior cervical ganglia in vitro, I will examine and quantify changes in the activities and amounts of the neurotransmitter enzymes with the changes in the neuronal membrane during axonal regeneration during the retrograde action. Using image analysis and immunocytochemial techniques, it will be prossible for the first time to directly compare changes in the cell's biochemistry with changes in its morphology. This study will also investigate the effect of facilitation and inhibition of axonal sprouting on the expression of the neurotransmitter enzymes. The long-term objective of this research is to provide information about the interrelationship between changes in the cell's morphology with changes in the cell's biochemistry. These findings should be useful in treatment of neuroblastoma as a cancer and also in understanding the processes and signals involved in neruonal regeneraton.